Clinical features and outcome in hospitalized heart failure in Japan (from the ATTEND Registry).

BACKGROUND: Hospitalized heart failure (HHF) is a critical issue in Japan. To improve its management and outcomes, the clinical features, in-hospital management, and outcomes should be analyzed to improve the guidelines for HHF. METHODS AND RESULTS: The acute decompensated heart failure syndromes (ATTEND) registry is the largest study of HHF in Japan. The present report covers the clinical features and in-hospital management of HHF patients. The data from 4,842 enrolled patients have demonstrated that most Japanese HHF patients are elderly, with new onset, and a history of hypertension and orthopnea on admission. During hospitalization, furosemide and carperitide were commonly used and the length of stay was extremely long (mean 30 days), with 6.4% in-hospital mortality. CONCLUSIONS: The findings of the present study suggest the following: (1) the focus for hypertensive elderly and diabetic patients should be on primary prevention of HHF,(2) more intensive management with noninvasive positive pressure ventilation should be performed at the urgent stage, (3) it is necessary to clarify the clinical benefit of carperitide and angiotensin-receptor blockers, because they are commonly used in Japan, and (4) it is necessary to clarify the relationship between in-hospital mortality and length of stay from the viewpoint of both outcome and cost of patient care.

Secondary preventive effects of a calcium antagonist for ischemic heart attack: randomized parallel comparison with ß-blockers.

BACKGROUND: Beta-blockers (BB) have been widely used in the management of hypertension and acute myocardial infarction (AMI), and both national and international guidelines have recommended them as first-line agents. Calcium channel antagonists (CCA) are also effective in the treatment of hypertension and angina pectoris. However, the efficacy of CCA in the prevention of cardiovascular events in post-myocardial infarction (MI) patients in comparison to that of BB remains unclear. METHODS AND RESULTS: A total of 120 post-MI patients (71 patients who were at least 1 month after the onset AMI and 49 stable coronary artery disease patients with a history of MI) were randomly assigned to receive a BB (atenolol, 25-50mg/day, n=60) or a CCA (benidipine, 4-8 mg/day, n=60). All patients with AMI within the previous 1 month or with vasospastic angina were excluded from the present study. The baseline clinical characteristics were generally similar in the BB and CCA groups. The rate of primary composite outcome was 26.3% in the BB group in comparison to 13.3% in the CCA group, with no significant between-group differences (hazard ratio with the CCA group 0.640, P=0.276). Both treatments were well tolerated with few severe adverse events. CONCLUSIONS: CCA treatment was found to be as effective as BB in reducing cardiovascular events in post-MI patients.

Acute decompensated heart failure syndromes (ATTEND) registry. A prospective observational multicenter cohort study: rationale, design, and preliminary data.

Acute heart failure syndromes (AHFS) are likely to increase in the future, and the high readmission rate of patients with AHFS is an important issue in Western countries. However, there are very few published epidemiological studies on AHFS in the Asia Pacific region. Because AHFS are heterogeneous, the characteristics, clinical profile, and management of AHFS should be clarified in an epidemiological study. The acute decompensated heart failure syndromes (ATTEND) registry is a prospective, observational, multicenter cohort study being performed in Japan and is the first epidemiological study of AHFS in the Asia Pacific region. This study is designed to investigate several aspects of AHFS as follows: (1) the registry allows patient-based data collection for precise evaluation of patient characteristics and short-term outcomes, including the readmission rate; (2) confirmation of clinical assessments can be performed, and new clinical assessments can be created; and (3) feedback allows the modification of guidelines for clinical management. The present report describes the clinical characteristics of patients with AHFS in Japan based on the preliminary data collected in this study, and the similarities and differences in characteristics of these patients compared with those in Western countries. Although most of the patient characteristics did not differ from those reported in Western studies, there are some unique findings in this study, including a high rate of treatment with carperitide (69.4%) and angiotensin II receptor blockers (53.9%) at discharge and a longer hospital stay (median 21 days). The ATTEND registry is designed to provide valuable information to clarify the characteristics of patients with AHFS to improve their management.

Urotensin II activates sarcolemmal Na+/H+ exchanger in adult rat ventricular myocytes.

OBJECTIVES: Our aims in the present study were (1) to determine the effects of urotensin II (UT-II) on the sarcolemmal Na/H exchanger (NHE1) activity, and (2) to investigate possible kinase pathways for UT-II-mediated NHE1 stimulation. METHODS: In single rat ventricular myocytes (n = 5-10/group) loaded with the pH-sensitive fluoroprobe carboxy-seminaphthorhodafluor-1, acid efflux rates (JH) were determined as an index of NHE1 activity by rate of recovery of intracellular pH (pHi) from NH4Cl-induced acidosis and the intrinsic buffering power. Phosphorylation of extracellular signal-regulated kinase (ERK), a key kinase of NHE1 activation, was determined by Western blot analysis. RESULTS: JH increased by 31%-71% relative to control in the presence of 100 nmol/L UT-II at pHi range of 6.6-7.0. Stimulation of NHE1 activity by UT-II was abolished by inhibitors of phospholipase C, protein kinase C, and ERK kinase; 2-nitro-4-carboxyphenil-N,N-diphenilcarbamate at 100 micromol/L, GF109203X at 300 nmol/L, and PD98059 at 50 micromol/L, respectively. Moreover, UT-II at 100 nmol/L produced a significant increase in cellular ERK1/2 phosphorylation, which was also inhibited by those inhibitors. CONCLUSIONS: Our study was the first to demonstrate that UT-II activates the cardiac sarcolemmal NHE1 and that the phenomenon may involve, at least in part, the phospholipase C-protein kinase C-ERK pathway.

Effects of a pure alpha/beta-adrenergic receptor blocker on monocrotaline-induced pulmonary arterial hypertension with right ventricular hypertrophy in rats.

BACKGROUND: It is unclear how much the sympathetic nervous system is involved in the development of pulmonary arterial hypertension (PAH). The present study examined whether or not a pure alpha/beta-adrenergic receptor blocker (arotinolol) could prevent the development of PAH and right ventricular hypertrophy (RVH) in a rat model of monocrotaline (MCT)-induced PAH. METHODS AND RESULTS: The heart rate, arterial blood pressure (BP), left ventricular pressure, pulmonary artery pressure (PAP), and right ventricular pressure (RVP) were measured after administration of arotinolol or saline for 2 weeks. Ventricular weight and myocyte size were also measured. Mean PAP was increased less in the arotinolol group (n=6), (53 +/-9 vs 21 +/-2 mmHg in the control (n=6); P<0.01). Systolic RVP was also less in the arotinolol group (41 +/-3 vs 91 +/-14 mmHg in the control, P<0.05) without differences in BP. It also significantly reduced the RV/body weight ratio (0.58 +/-0.01 vs 0.77 +/-0.04 mg/g; P<0.01). Furthermore, the myocyte width was significantly decreased in the arotinolol group. CONCLUSIONS: The pure alpha/beta-blocker arotinolol prevented the progression of MCT-induced PAH and RVH in rats, suggesting that sympathetic nervous activation might play a role in the development of PAH.

Administration of the Rho-kinase inhibitor, fasudil, following nitroglycerin additionally dilates the site of coronary spasm in patients with vasospastic angina.

BACKGROUND: The Rho/Rho-kinase signaling pathway is known to be involved in the pathogenesis of coronary artery spasm. Previous studies reported the efficacy of the Rho-kinase inhibitor, fasudil, in the prevention and relief of coronary spasm. The usefulness of fasudil in combination with conventional vasodilating agents, however, has not been fully examined in patients with vasospastic angina. METHODS AND RESULTS: A total of 26 patients (mean age, 61+/-11 years) with documented vasospasm in the left anterior descending coronary artery were examined by the acetylcholine stress test. Coronary diameter at the spasm site was measured at baseline and after the administration of vasodilator agents in the following order: intracoronary nitroglycerin (NTG) (300 microg), intravenous fasudil (30 mg, n=15, fasudil group) or saline (n=11, saline group), and again NTG during coronary angiography. The increase in diameter observed following the first NTG administration was found to be similar in the fasudil and saline groups (38.3+/-23.5% and 42.3+/-17.1%, respectively). The additional change in diameter on fasudil treatment (16.9+/-11.2% increase over the diameter after the first NTG administration) was significantly larger than that with saline (-2.8+/-7.6%, P<0.001). The second administration of NTG did not affect the diameter of the spasm site in either group. CONCLUSIONS: Fasudil further dilated the site of coronary spasm, which had already been treated with NTG in patients with vasospastic angina. These findings support and extend the previous results that showed the feasibility of employing fasudil as a novel therapeutic approach for coronary spasm.

Cytokine levels in pleural effusions of patients under intensive care.

BACKGROUND: Pleural effusions develop for various reasons in patients admitted to intensive care units (ICUs). To understand why this occurs is important, yet cytokine levels in pleural effusions have rarely been measured from a cardiovascular viewpoint. OBJECTIVE: To understand the characteristics of pleural cytokines in patients admitted to the ICU. METHODS: The subjects were 43 patients with pleural effusion who were admitted to the ICU from June 2001 through March 2006. We divided the patients into transudate (n=23) and exudate (n=20) groups. We measured levels of interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-alpha in pleural effusions and peripheral blood and evaluated their relationships with body temperature, C-reactive protein (CRP) level, and the peripheral white blood cell (WBC) count. RESULTS: Levels of pleural IL-6 were significantly higher and levels of TNF-alpha tended to be higher in pleural effusions from the exudate than in those from the transudate group (3,350+/-3,627 vs. 1,677+/-1,086 pg/m and 6.6+/-3.4 vs. 4.8+/-2.6 pg/mL, respectively). However, in both groups levels of IL-10 in pleural effusions were similar to those in serum and levels of IL-6 were significantly higher in pleural effusion than in serum. Serum IL-6 levels correlated with inflammatory markers (CRP and body temperature), whereas cytokines in pleural effusion did not correlate with any of these markers (body temperature, CRP, and WBC). CONCLUSION: Pleural levels of IL-6 were significantly higher in the exudate group than in the transudate group but did not correlate with serum levels of IL-6 or with systemic inflammatory markers. These findings suggest that pleural IL-6 levels correlate with local lung or pleural inflammation in patients admitted to the ICU.

9-Year Trend in the Management of Acute Heart Failure in Japan: A Report From the National Consortium of Acute Heart Failure Registries.

Background Acute heart failure ( AHF ) is a heterogeneous condition, and its characteristics and management patterns differ by region. Furthermore, limited evidence is available on AHF outside of Western countries. A project by the National Consortium of Acute Heart Failure Registries was designed to evaluate the trends over time in patient backgrounds, in-hospital management patterns, and long-term outcomes of patients with AHF over 9 years in Japan. Methods and Results Between 2007 and 2015, registry data for patients with AHF were collected from 3 large-scale quality AHF registries ( ATTEND / WET - HF / REALITY - AHF ). Predefined end points were trends over time in age, sex, and clinical outcomes, including short- and long-term mortality and readmission for heart failure. The final data set consisted of 9075 patients with AHF . No significant differences in patient backgrounds and laboratory findings (eg, anemia or renal function) were observed, with the exception of patient age; mean age became substantially higher over 9 years (71.6-77.0 years; P for trend, <0.001). On the contrary, length of hospital stay became shorter (mean, 26-16 days). These changes were not associated with in-hospital mortality (4.7-7.5%) or 30-day heart failure readmission rate (4.8-5.4%), as well as 1-year mortality and heart failure readmission rate (20.1-23.3% and 23.6-26.2%, respectively). Conclusions Length of hospital stay in patients with AHF shortened over the 9-year period despite the increasing age of the patients. However, short- and long-term outcomes do not seem to be affected; continuous efforts to monitor clinical outcomes in patients with AHF are needed.

Trends and predictors of non-cardiovascular death in patients hospitalized for acute heart failure.

BACKGROUND: Little information is available on non-cardiovascular (CV) death in acute heart failure (AHF) patients. The present study determined the incidence, time course, and factors associated with long-term non-CV death in AHF patients in a real-world setting. METHODS: The ATTEND registry, a nationwide, prospective observational multicenter cohort study, included 4842 consecutive patients hospitalized for AHF. The primary endpoint of the present study was non-CV death. RESULTS: Median follow-up duration from admission was 513 (range, 385-778) days. Over the study period, 1183 patients died; 356 deaths (30.1%) were non-CV related. The proportion of non-CV deaths increased in the later follow-up phase (0-180days, 26.7%; 181-360days, 38.4%; >360days, 36.6%, p<0.001). After adjustment for all variables at baseline, age (hazard ratio [HR] 1.6 per decade, p<0.001) and non-cardiac comorbidities including chronic obstructive pulmonary disease (HR 1.58, p=0.003), history of stroke (HR 1.44, p=0.011), renal insufficiency (HR 1.07, per 10ml/min/1.73m2 decrease in estimated glomerular filtration, p=0.015), and hemoglobin (HR 1.15 per 1.0g/dl decrease, p<0.001) were strongly associated with non-CV death. Other predictors included ischemic etiology (HR 1.33, p=0.023), prior hospitalization for heart failure (HR 1.34, p=0.017), C-reactive protein (HR 1.04, p<0.001), and statin use (HR 0.70, p=0.016). CONCLUSIONS: The incidence of non-CV death was high in patients with AHF, accounting for 30% of long-term mortality. Furthermore, the proportion of non-CV death increased in the later follow-up phase. Better understanding of non-CV death and more comprehensive treatment of non-CV comorbidities are vital to further improving prognosis in AHF patients.

Controlled release of basic fibroblast growth factor promotes healing of the pancreaticojejunal anastomosis: a novel approach toward zero pancreatic fistula.

BACKGROUND: Several reconstructive surgical techniques have been proposed for restoring pancreatico-jejunal continuity. Little has been done, however, to evaluate the efficacy of tissue engineering on anastomotic healing. We examined the effects of basic fibroblast growth factor (bFGF) incorporated in gelatin hydrogel (GH) microspheres on the anastomotic healing of pancreaticojejunostomy. METHODS: As a preliminary experiment, 20 female Wistar rats received a jejunal subserosal injection of 1 microg of bFGF-GH (n = 10), 1 microg of Free-bFGF (n = 5), or gelatin alone (n = 5) to study the effects of bFGF on the histology of normal jejunum on day 7 after the injection. Next, 12 beagle dogs received a jejunal subserosal injection of 100-microg bFGF-GH (n = 7) or gelatin alone (n = 5) at the anastomotic site of pancreaticojejunostomy. Four types of assessment were performed to compare the 2 groups: pancreatography, breaking strength test, pathologic examination, and calculation of the microvessel density (MVD). RESULTS: The bFGF-GH injection led to markedly increased levels of collagen and fibroblastic cellularity in the subserosal layer of the Wistar rats. In contrast, the rats treated by gelatin alone exhibited no such effects. No anastomotic failures were observed in the dogs treated by bFGF-GH. Histologic observations of this group revealed abundant granulation tissues. Treatment with bFGF-GH significantly increased the breaking strength and MVD over the levels measured in the control group (P < .01). CONCLUSIONS: bFGF-GH accelerates healing of pancreaticojejunal anastomosis during the early postoperative period. Basic FGF-GH may show promise as a new technique for preventing anastomotic failure of pancreaticojejunostomy.

Transduction of anti-cell death protein FNK protects isolated rat hearts from myocardial infarction induced by ischemia/reperfusion.

Artificial anti-cell death protein FNK, a Bcl-x(L) derivative with three amino acid-substitutions (Y22F, Q26N, and R165K) has enhanced anti-apoptotic and anti-necrotic activity and facilitates cell survival in many species and cell types. The objectives of this study were (i) to investigate whether the protein conjugated with a protein transduction domain (PTD-FNK) reduces myocardial infarct size and improves post-ischemic cardiac function in ischemic/reperfused rat hearts, and (ii) to understand the mechanism(s) by which PTD-FNK exerts a protective effect. Isolated rat hearts were subjected to 35-min global ischemia, followed by 120-min reperfusion using the Langendorff methods. PTD-FNK (a total of 30 microl) was injected intramuscularly into the anterior wall of the left ventricle either at 1 min after induction of global ischemia (group A) or at 30 min after induction of global ischemia (at 5 min before reperfusion) (group B). In group A, infarct size was significantly reduced from 47.8+/-6.8% in the control to 30.4+/-5.2, 28.7+/-3.8, and 30.4+/-6.8% with PTD-FNK at 5, 50, and 500 nmol/l, respectively (p<0.05). Temporal recovery of left ventricular developed pressure at 60 min and 120 min after reperfusion was significantly better in PTD-FNK (50 and 500 nmol/l)-treated groups than in the control (p<0.05). In contrast, PTD-FNK treatment had no effect on group B. Western blot analysis showed that PTD-FNK markedly inhibited procaspase-3 cleavage (activation of caspase-3) and reduced the number of nuclei stained by a terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphoshate nick-end labeling (TUNEL) assay. These findings suggest that PTD-FNK reduces the volume of myocardial infarction with corresponding functional recovery, at least in part, through the suppression of myocardial apoptosis following ischemia/reperfusion.

Analysis of alteration of blood pressure response to exercise through baroreflex.

BACKGROUND: The baroreflex has been reported to play an important role in hemodynamic regulation during exercise. Therefore, impairment of baroreflex function can induce an abnormal response of systolic blood pressure (SBP) to exercise, including exercise-induced hypertension. To clarify whether baroreflex function alters SBP response, we examined the relationship of baroreflex sensitivity (BRS) with SBP response to exercise. METHODS: In 22 subjects without cardiac dysfunction, BRS (ms/mmHg) was measured by the phenylephrine method, and a treadmill exercise test was administered according to Bruce's protocol. RESULTS: 1) The chronotropic response to exercise was higher in the normal BRS group than in the reduced BRS group (p<0.01). The SBP at the initial phase of exercise (1 min after the start of exercise) showed a smaller increase in the normal BRS group than in the reduced BRS group (p<0.01). During the initial phase of exercise, BRS had negative correlation with the SBP increment from rest (r=-0.408, p<0.05). During submaximal exercise (6 min after the start of exercise), a positive correlation between BRS and SBP response (r=0.422, p<0.05) was shown. 2) Subjects were divided into 2 groups: 12 subjects with normal BRS (> or =5 ms/mmHg) and 10 subjects with reduced BRS (<5 ms/mmHg). During the initial exercise phase, the negative correlation between BRS and SBP response was stronger in the normal BRS group (r=-0.398) than in the reduced BRS group (r= -0.126). During submaximal exercise, BRS had a positive correlation with BP response to exercise in subjects with normal BRS (r=0.462). CONCLUSION: Preserved baroreflex function is thought to be related to the pressor response to submaximal exercise, although the baroreflex is thought to be associated with the stabilization of blood pressure change during the initial exercise phase. These findings suggest that exercise-induced hypertension develops through the baroreflex mechanism.

Relationship between plasma norepinephrine at peak exercise and 123I-MIBG imaging of the heart and lower limbs in heart failure.

BACKGROUND: Past studies suggested that plasma norepinephrine during exercise originates in sympathetic nerve endings and that the main origin differs among pathophysiological conditions. AIMS: This study investigated the most important site of sympathetic terminals as an origin of plasma norepinephrine during exercise in patients with heart failure using (123)I- metaiodobenzylguanidine (MIBG) scintigraphy. METHODS AND RESULTS: Twenty patients with organic heart disease underwent exercise testing and (123)I-MIBG scintigraphy. Systemic (123)I-MIBG uptake was measured 4 hours after (123)I-MIBG injection, and the heart-to-brain (H/B) and lower limb-to-brain ratios (L/B) were calculated. Plasma norepinephrine concentration was measured at rest and at peak exercise. Subjects were divided into two groups: those with preserved left ventricular ejection fraction (LVEF> or =45%, n=8) and those with reduced LVEF (<45%, n=12). Plasma norepinephrine at rest did not correlate with H/B or L/B. In the preserved LVEF group, plasma norepinephrine at peak exercise was correlated with H/B (r=0.722), but not with L/B. In the reduced LVEF group, the norepinephrine response to peak exercise correlated with L/B (r=0.642), but not with H/B. CONCLUSION: The present findings suggest that norepinephrine concentration is regulated by sympathetic terminal function of working muscles in patients with impaired LVEF and by that of the heart in patients with preserved LVEF.

Dynamics and source of endothelin-1 and interleukin-6 following coronary reperfusion in patients with acute myocardial infarction.

OBJECTIVES: The goals of this study were to determine the source of circulating endothelin-1 (ET-1) and interleukin-6 (IL-6) in acute myocardial infarction (MI) and to study the effects of coronary reperfusion (CR) on plasma levels of ET-1 and IL-6. METHODS: We serially measured plasma concentrations of ET-1 and IL-6 at different sampling sites before and after CR in patients with acute MI. A femoral vein (FV) catheter, a Swan-Ganz catheter, and a femoral artery (FA) catheter were placed in 25 patients with acute MI who were admitted within 12 hours after onset. For the measurement of ET-1 and IL-6 concentrations, blood samples from the FV, right atrium (RA), pulmonary artery (PA), and FA were collected before and 1 hour, 8 hours, and 24 hours after CR therapy. In 5 of the 25 patients, blood samples were collected through a coronary sinus (CS) catheter. We also assessed the gradient across 3 vascular beds (systemic, pulmonary, and coronary) as indices of the net release of ET-1 and IL-6 from those vascular beds. The maximal serum creatine kinase (CK) levels were assessed as an index of myocardial necrosis. RESULTS: ET-1 levels were higher in the FV than in the RA, PA, or FA. On CR, ET-1 levels peaked after 1 hour and returned to baseline by 24 hours. Calculated net release of ET-1 from the systemic vascular bed (ET-1 at FV-ET-1 at FA) was the highest among the 3 vascular beds. Plasma ET-1 levels correlated with hemodynamic parameters. Plasma IL-6 levels were similar among different sampling sites, whereas calculated net release of IL-6 from the coronary vascular bed was the highest among the 3 vascular beds. IL-6 levels increased throughout 24 hours after coronary reperfusion and closely correlated with maximal CK levels. CONCLUSIONS: The present study suggests that, in acute MI, the major source of ET-1 maintaining baseline plasma levels is the systemic vascular bed and that the ET-1 levels presumably reflect the congestion. ET-1 levels peaked 1 hour after CR. IL-6 increased for 24 hours after CR. The major source of IL-6 is the coronary vascular bed. Only a slight correlation was observed between plasma ET-1 and IL-6 levels.

Hemiplegia recovers after cranioplasty in stroke patients in the chronic stage.

We evaluated quantitatively the recovery from impairment and disability in hemiplegic stroke survivors who received cranioplasty in the chronic stage. Seven first-ever stroke survivors with hemiplegia (mean age 56+/-3 years) who required delayed (3-9 months after the onset) cranioplasty during continuous rehabilitation therapy were studied. Recovery grade (1-12) of hemiplegia and Barthel index were assessed monthly before (the first rehabilitation) and after the cranioplasty (the second rehabilitation). The recovery grade of upper and lower extremity movements significantly increased both in the first and in the second rehabilitation. Changes in the upper and lower extremity grades were significantly larger in the second rehabilitation (1.0+/-0.3 in the first vs. 2.4+/-0.7 in the second rehabilitation for upper extremity, P=0.007; 1.4+/-0.4 in the first vs. 3.4+/-0.7 in the second rehabilitation for lower extremity, P=0.002). Increase in the Barthel index was larger in the second rehabilitation (23+/-8 in the first vs. 33+/-5 in the second rehabilitation); all patients regained the ability to walk. Significant recovery of functional grade and recovery from disability occurred after the cranioplasty in the chronic stage (>or=3 months) of stroke.

Relationship of renal insufficiency and clinical features or comorbidities with clinical outcome in patients hospitalised for acute heart failure syndromes.

BACKGROUND: Renal insufficiency is a well-known predictor of adverse events in patients with acute heart failure syndromes (AHFS). However, it remains unclear whether there are subgroups of AHFS patients in whom renal insufficiency is related to a higher risk of adverse events because of the heterogeneity of this patient population. Therefore, we investigated the relationship between renal insufficiency, clinical features or comorbidities, and the risk of adverse events in patients with AHFS. METHODS AND RESULTS: Of 4842 patients enrolled in the Acute Decompensated Heart Failure Syndromes (ATTEND) registry, 4628 patients (95.6%) were evaluated in the present study in order to assess the relationship of renal insufficiency and clinical features or comorbidities with all-cause mortality after admission. Renal insufficiency was defined as an estimated creatinine clearance of ⩽40 mL/min (calculated by the Cockcroft-Gault formula) at admission. The median follow-up period after admission was 524 (391-789) days. The all-cause mortality rate after admission was significantly higher in patients with renal insufficiency (36.7%) than in patients without renal insufficiency (14.4%). Stratified analysis was performed in order to explore the heterogeneity of the influence of renal insufficiency on all-cause mortality. This analysis revealed that an ischaemic aetiology and a history of diabetes, atrial fibrillation, serum sodium, and anaemia at admission had significant influences on the relationship between renal insufficiency and all-cause mortality. CONCLUSIONS: The present study demonstrated that the relationship between renal insufficiency and all-cause mortality of AHFS patients varies markedly with clinical features or comorbidities and the mode of presentation due to the heterogeneity of this patient population.

C-reactive protein level on admission and time to and cause of death in patients hospitalized for acute heart failure.

Aims: We analysed the association between C-reactive protein (CRP) levels measured on admission and timing and cause of death among patients hospitalized for acute heart failure (AHF). Methods and Results: The ATTEND study prospectively registered 4777 hospitalized AHF patients with data on CRP levels on admission. Mortality risks were assessed by univariable and multivariable Cox proportional and non-proportional hazards models. The overall median CRP level was 5.8 mg/L (intertertile range: 2.9-11.8 mg/L). There were significant increases in all-cause, cardiac, and non-cardiac mortalities from the lowest to highest CRP tertiles throughout the follow-up periods. Within 120 days after admission, CRP levels in the highest tertile (>11.8 mg/L) were independently associated with higher all-cause (hazard ratio [HR], 2.21; 95% confidence interval [CI], 1.69-2.88; P < 0.001), cardiac (HR, 1.88; 95% CI, 1.37-2.58; P < 0.001), and non-cardiac (HR, 3.21; 95% CI, 1.94-5.32; P < 0.001) deaths, while levels in the second tertile (2.9-11.8 mg/L) were not associated with poorer survival, compared with levels in the first tertile (<2.9 mg/L). However, in terms of cardiac death, the hazard ratios for patients in the third tertile decreased markedly with time and only CRP levels in second tertile were independently associated with poorer cardiac survival after the follow-up period of 120 days (HR, 1.44; 95% CI, 1.09-1.89; P = 0.011). Conclusions: Markedly elevated CRP levels at admission in patients with AHF may be associated with higher short-term cardiac and non-cardiac mortalities. In addition, modestly elevated CRP levels may be associated with higher mortality, especially cardiac mortality, after 120 days of long-term follow-up.

Incidence and predictors of in-hospital non-cardiac death in patients with acute heart failure.

BACKGROUND: Patients with acute heart failure (AHF) commonly have multiple co-morbidities, and some of these patients die in the hospital from causes other than aggravated heart failure. However, limited information is available on the mode of death in patients with AHF. Therefore, the present study was performed to determine the incidence and predictors of in-hospital non-cardiac death in patients with AHF, using the Acute Decompensated Heart Failure Syndromes (ATTEND) registry Methods: The ATTEND registry included 4842 consecutive patients with AHF admitted between April 2007-September 2011. The primary endpoint of the present study was in-hospital non-cardiac death. A stepwise regression model was used to identify the predictors of in-hospital non-cardiac death. RESULTS: The incidence of all-cause in-hospital mortality was 6.4% ( n=312), and the incidence was 1.9% ( n=93) and 4.5% ( n=219) for non-cardiac and cardiac causes, respectively. Old age was associated with in-hospital non-cardiac death, with a 42% increase in the risk per decade (odds 1.42, p=0.004). Additionally, co-morbidities including chronic obstructive pulmonary disease (odds 1.98, p=0.034) and anaemia (odds 1.17 (per 1.0 g/dl decrease), p=0.006) were strongly associated with in-hospital non-cardiac death. Moreover, other predictors included low serum sodium levels (odds 1.05 (per 1.0 mEq/l decrease), p=0.045), high C-reactive protein levels (odds 1.07, p<0.001) and no statin use (odds 0.40, p=0.024). CONCLUSIONS: The incidence of in-hospital non-cardiac death was markedly high in patients with AHF, accounting for 30% of all in-hospital deaths in the ATTEND registry. Thus, the prevention and management of non-cardiac complications are vital to prevent acute-phase mortality in patients with AHF, especially those with predictors of in-hospital non-cardiac death.

Novel mechanism of postinfarction ventricular tachycardia originating in surviving left posterior Purkinje fibers.

BACKGROUND: Other than bundle branch reentry and interfascicular reentry, monomorphic postmyocardial infarction (post-MI) reentrant ventricular tachycardia (VT) including the His-Purkinje system has not been reported. Verapamil-sensitive idiopathic left VT includes the left posterior Purkinje fibers but develops in patients without structural heart disease. OBJECTIVES: The purpose of this study was to describe a novel mechanism of reentrant VT arising from the left posterior Purkinje fibers in patients with a prior MI. METHODS: The study consisted of four patients with a prior MI and symptomatic heart failure who underwent electrophysiologic study and catheter ablation for VT showing right bundle branch block (n = 3) or atypical left bundle branch block (n = 1) morphology with superior axis. In two patients, the VT frequently emerged during the acute phase of MI and required emergency catheter ablation. RESULTS: Clinical VT was reproducibly induced by programmed stimulation. In three patients, both diastolic and presystolic Purkinje potentials were sequentially recorded along the left ventricular posterior septum during the VT, whereas in the fourth patient, only presystolic Purkinje potentials were observed. During entrainment pacing from the right atrium, diastolic Purkinje potentials were captured orthodromically and demonstrated decremental conduction properties, whereas presystolic Purkinje potentials were captured antidromically and appeared between the His and QRS complex. Radiofrequency energy delivered at the site exhibiting a Purkinje-QRS interval of 58 +/- 26 ms successfully eliminated the VTs without provoking any conduction disturbances. CONCLUSION: Reentrant monomorphic VT originating from the left posterior Purkinje fibers, which is analogous to idiopathic left VT, can develop in the acute or chronic phase of MI. Catheter ablation is highly effective in eliminating this VT without affecting left ventricular conduction.

High-frequency potentials developed in wavelet-transformed electrocardiogram as a novel indicator for detecting Brugada syndrome.

BACKGROUND: A reliable alternative method for detecting Brugada syndrome is desirable because the diagnosis of Brugada syndrome using 12-lead ECG is not optimal. OBJECTIVES: The purpose of this study was to assess the usefulness of the wavelet-transformed ECG in detecting Brugada syndrome. METHODS: The study consisted of 15 patients with Brugada syndrome and 15 healthy subjects (control group). The parameters on the signal-averaged ECG and the frequency components recorded from the wavelet-transformed ECG were compared between the two groups. Measurements were repeated after pilsicainide infusion in the two groups of patients, after an isoproterenol infusion following pilsicainide injection, and after administration of cilostazol in the group of patients with Brugada syndrome. RESULTS: The positive rate of late potentials was 80% in the Brugada syndrome group and 0% in the control group (P <.01). The high-frequency components (80-150 Hz) were developed in the Brugada syndrome group to a greater extent than in the control group, but the low-frequency components (10-50 Hz) did not differ (mean peak power at 80 Hz; 713 +/- 36 vs 488 +/- 60, P <.001). After pilsicainide injection, high-frequency components significantly increased in both groups. However, after isoproterenol and cilostazol administration, high-frequency components significantly decreased but remained higher than in the control group (80 Hz; 655 +/- 40 vs 488 +/- 60, P <.001). The sensitivity of the development of high-frequency components in detecting Brugada syndrome was higher than that of signal-averaged ECG (100% vs 80%), but specificity remained high and similar (100% for both methods). CONCLUSION: Abnormally high-frequency components recorded from the wavelet-transformed ECG might be a novel factor in detecting Brugada syndrome.